Blur adaptation: clinical and refractive considerations

The human visual system is amenable to a number of adaptive processes; one such process, or collection of processes, is the adaptation to blur. Blur adaptation can be observed as an improvement in vision under degraded conditions, and these changes occur relatively rapidly following exposure to blur. The potential important future directions of this research area and the clinical implications of blur adaptation are discussed.     

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.     

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

Training the Anesthesiologist Trainer: Enhancing the Quality of Feedback during Human Patient Simulations

An essential piece of anesthesiologist training is attending resident feedback sessions. Yet, few attending anesthesiologists have formal teaching education and little time to acquire it. In this field experiment, attending physicians were randomly assigned to a control group or to receive 30 minutes of feedback training inspired by Implicit Person Theory (IPT). As such, IPT training encouraged physicians to praise process-oriented learning while discouraging performance-oriented mindsets. Attending physicians then observed residents participate in a human patient simulation (HPS) activity and provided residents with feedback. Content and statistical analyses revealed trained attending physicians praised learning goals and challenged performance goals more often than untrained physicians during feedback sessions. Thus, the training provides a rapid method of enhancing the quality of attending physicians’ training communication.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.